The use of opioids in therapy dates to the Neolithic, and their effectiveness for pain treatment, as euphoragens, and their addictiveness has made them central to medicine, commerce, and conflict ever since. Their addictiveness and potentially lethal side effects, such as respiratory depression, have driven campaigns to improve them since the 19th century, with the purification of morphine and codeine and the synthesis of heroin. Recently, molecular studies have in fact suggested that the CNS-based analgesia relates to μ opioid receptor signaling through the Gi-protein pathway, while many of the pathophysiologies of the opioid drugs, including respiratory depression and constipation, is conferred via arrestin pathway signaling. Identifying agonists specific to μ opioid receptors and biased toward the Gi-protein pathway have thus far remained elusive. Disclosed herein, inter alia, are solutions to these and other problems in the art.